Multimerin 1 supports platelet function in vivo and binds to specific GPAGPOGPX motifs in fibrillar collagens that enhance platelet adhesion.
J Thromb Haemost
; 19(2): 547-561, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-33179420
ABSTRACT
BACKGROUND:
Multimerin 1 (human MMRN1, mouse Mmrn1) is a homopolymeric, adhesive, platelet and endothelial protein that binds to von Willebrand factor and enhances platelet adhesion to fibrillar collagen ex vivo.OBJECTIVES:
To examine the impact of Mmrn1 deficiency on platelet adhesive function, and the molecular motifs in fibrillar collagen that bind MMRN1 to enhance platelet adhesion.METHODS:
Mmrn1-deficient mice were generated and assessed for altered platelet adhesive function. Collagen Toolkit peptides, and other triple-helical collagen peptides, were used to identify multimerin 1 binding motifs and their contribution to platelet adhesion.RESULTS:
MMRN1 bound to conserved GPAGPOGPX sequences in collagens I, II, and III (including GPAGPOGPI, GPAGPOGPV, and GPAGPOGPQ) that enhanced activated human platelet adhesion to collagen synergistically with other triple-helical collagen peptides (P < .05). Mmrn1-/- and Mmrn1+/- mice were viable and fertile, with complete and partial platelet Mmrn1 deficiency, respectively. Relative to wild-type mice, Mmrn1-/- and Mmrn1+/- mice did not have overt bleeding, increased median bleeding times, or increased wound blood loss (P ≥ .07); however, they both showed significantly impaired platelet adhesion and thrombus formation in the ferric chloride injury model (P ≤ .0003). Mmrn1-/- platelets had impaired adhesion to GPAGPOGPX peptides and fibrillar collagen (P ≤ .03) and formed smaller aggregates than wild-type platelets when captured onto collagen, triple-helical collagen mimetic peptides, von Willebrand factor, or fibrinogen (P ≤ .008), despite preserved, low shear, and high shear aggregation responses.CONCLUSIONS:
Multimerin 1 supports platelet adhesion and thrombus formation and binds to highly conserved, GPAGPOGPX motifs in fibrillar collagens that synergistically enhance platelet adhesion.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Sanguíneas
/
Adhesividad Plaquetaria
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá